Research Perspective Volume 16, Issue 14 pp 11128—11133

Figure 1. Overview of drivers of GluCer accumulation, which leads to cellular senescence in dopaminergic neurons. Aging, stress, lysosomal dysfunction, decreased levels of GBA, and the regulation of GBA by reactive dopamine have all been shown to lead to the accumulation of glucocerebrosides (GluCer). We have recently shown that the accumulation of GluCer directly drives senescence of dopaminergic (DA) neurons, indicated by lysosomal accumulation, mitochondrial dysfunction, elevated senescence-associated ß-galactosidase, increased p21/p16 expression, and SASP factor upregulation (representative diagrams and images are modified from our previous study [10]).